Research Paper Volume 11, Issue 2 pp 501—522

Prognostic value of immune checkpoint molecules in head and neck cancer: a meta-analysis

Yi-Qun Jia1, *,, Bo Yang1, *,, Li-Ling Wen1, , Wen-Xin Mu1, , Zhi Wang1, , Bin Cheng1, ,

  • 1 Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China
* Equal contribution

Received: September 4, 2018       Accepted: January 1, 2019       Published: January 22, 2019
How to Cite

Copyright: Jia et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Immune checkpoint molecules are important targets in cancer immunotherapy, but their association with prognosis in patients with head and neck cancer is controversial. In this meta-analysis, we searched for 12 immune checkpoint molecules in the PubMed, Embase and Cochrane Library databases and retrieved 52 studies with 7127 participants. Among the molecules included in the search, indoleamine 2, 3-dioxygenase (IDO), programmed death ligand 1 (PD-L1), and programmed death 1 (PD-1) met the inclusion criteria for further analysis. Higher expression of IDO was associated with poorer overall survival in head and neck cancer patients (P = 0.011), but higher expression of PD-L1 correlated with better overall survival specifically in nasopharyngeal carcinoma patients (P = 0.01). In a sensitivity analysis, higher PD-L1 expression correlated with better progression-free survival (P = 0.043), and was associated with better overall survival in Caucasian subjects (P = 0.02), nasopharyngeal carcinoma patients (P = 0.015), and studies with small sample sizes (P = 0.001). PD-1 had no prognostic significance. There was no publication bias affecting the results. Thus, among the immune checkpoint molecules, IDO and PD-L1 are potential prognostic predictors in head and neck cancer.


PD-L1: programmed death ligand 1; PD-1: programmed death 1; LAG-3: lymphocyte activation gene 3; CTLA-4: cytotoxic T-lymphocyte-associated protein 4; PD-L2: programmed death ligand 2; IDO: indoleamine 2, 3-dioxygenase; VISTA: V-domain Ig suppressor of T cell activation; HR: hazard ratio; M/F: male/female; NA: not available; HNC: head and neck cancer; HNSCC: head and neck squamous cell carcinoma; OSCC: oral squamous cell carcinoma; NPC: nasopharyngeal carcinoma; OPSCC: oropharyngeal squamous cell carcinoma; LSCC: laryngeal squamous cell carcinoma; cut-off value: the value that can be diagnosed as positive/high expression of an immune checkpoint molecule; AQUA: automated quantitative analysis; IHC: immunohistochemistry; IF: immunofluorescence; qRT-PCR: quantitative reverse transcription polymerase chain reaction; FACS: fluorescence-activated cell sorting; FISH: fluorescence in situ hybridization; OS: overall survival; PFS: progression-free survival; DFS: disease-free survival; DSS: disease-specific survival; DMFS: distant metastases-free survival; P: prospective; NOS: Newcastle–Ottawa Quality Assessment Scale; CI: confidence interval.